Cerebrospinal Fluid Alpha-Synuclein Improves the Differentiation between Dementia with Lewy Bodies and Alzheimer's Disease in Clinical Practice

脑脊液α-突触核蛋白可提高临床实践中路易体痴呆和阿尔茨海默病鉴别诊断的准确性。

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Abstract

Background: Alpha-synuclein, abnormally aggregated in Dementia with Lewy Bodies (DLB), could represent a potential biomarker to improve the differentiation between DLB and Alzheimer’s disease (AD). Our main objective was to compare Cerebrospinal Fluid (CSF) alpha-synuclein levels between patients with DLB, AD and Neurological Control (NC) individuals. Methods: In a monocentric retrospective study, we assessed CSF alpha-synuclein concentration with a validated ELISA kit (ADx EUROIMMUN) in patients with DLB, AD and NC from a tertiary memory clinic. Between-group comparisons were performed, and Receiver Operating Characteristic analysis was used to identify the best CSF alpha-synuclein threshold. We examined the associations between CSF alpha-synuclein, other core AD CSF biomarkers and brain MRI characteristics. Results: We included 127 participants (mean age: 69.3 ± 8.1, Men: 41.7%). CSF alpha-synuclein levels were significantly lower in DLB than in AD (1.28 ± 0.52 ng/mL vs. 2.26 ± 0.91 ng/mL, respectively, p < 0.001) without differences due to the stage of cognitive impairment. The best alpha-synuclein threshold was characterized by an Area Under the Curve = 0.85, Sensitivity = 82.0% and Specificity = 76.0%. CSF alpha-synuclein was associated with CSF AT(N) biomarkers positivity (p < 0.01) but not with hippocampal atrophy or white matter lesions. Conclusion: CSF Alpha-synuclein evaluation could help to early differentiate patients with DLB and AD in association with existing biomarkers.

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